Cycle of Krebs

The cycle of tricarboxylic Krebs or cycle of the acids or cycle of the citric acid (citrate) is in the center of the cellular Métabolisme. He was discovered by the biologist Hans Adolf Krebs in 1937.

He is the final and common point Catabolisme of the Glucide S, Lipide S and protid S.

The principal function of this reactional sequence of cyclic nature is the oxidation of the groupings Acétyl coming from the Pyruvate and which enter the cycle in the form of Acetyl-coA (acétylcoenzyme A).

Once degraded by the Glycolysis, the Way of pentoses phosphates or sees it Entner-Doudoroff, the Glucose in Pyruvate is transformed into acétylcoenzyme has and oxaloacétate. These two made up is the starting point of the cycle of Krebs which will be condensed in Citrate (from where the name of the cycle).

The cycle of Krebs proceeds in the matrix of the Mitochondrie, in Aérobiose. The Enzyme S catalyzing this continuation of reactions are localized in the matrix mitochondriale or on the level of the membrane mitochondriale interns.

With the respiratory Chain, the cycle of Krebs is the ultimate process of degradation of different the metabolites which will be degraded in Carbon dioxide and Eau.

Stages of the cycle of Krebs

Synthesis of citrate

The irreversible reaction of condensation is catalyzed by the citrate Synthase but presents a transitory intermediary: the cytroyl CoA.

Dehydration of citrate

This reaction of reversible dehydration, catalyzed by a Lyase (cis-aconitase), produced cis-aconitate (or better: Z-aconitate). Although the citrate seems to be symmetrical, one could show that the departure of Eau takes place between carbons of the oxaloacétate.

Hydration of the cis-aconitate

This reaction reversible and is consequently catalyzed Enzyme that at the preceding stage. The addition of Eau on the double connection takes place in a different position: it is the isocitrate.

Oxidation of the isocitrate

This reversible reaction is catalyzed by a Oxydoréductase, the Isocitrate déshydrogénase.

Decarboxylation of the oxalosuccinate

There is release of the Carbon dioxide during this irreversible and spontaneous reaction, the oxalosuccinate being an unstable compound.

Oxydative decarboxylation of the α-cétoglutarate

This reaction is the same one as that allowing the passage of the Pyruvate the acétylCoA. The enzymatic complex utilizes 5 coenzymes successive (Thiamine pyrophosphate or TPP), the Lipoate, NAD, the Coenzyme has and FAD. This reaction is irreversible.

Formation of succinate

During this reaction, there is transfer of the energy of the succinylcoenzyme has (by its connection acylthioester) with the Guanosine diphosphate. This reversible reaction is catalyzed by a Transférase, succinate thiokinase. Formation of a connection ~P (GTP in the animals and ATP at the plants)

Oxidation of succinate

This reaction is catalyzed by a flavoproteic Enzyme with FAD, inhibited by the malonate, succinate déshydrogénase (Oxydoréductase).

Hydration of the fumarate

This reaction of addition is catalyzed by a Lyase, the fumarase.

Oxidation of the malate: closing of the cycle

This reaction closes again the cycle. There is formation of oxaloacétate catalyzed by the malate déshydrogénase (Oxydoréductase).

Average Mnemotechnics

If the citr one Iso the acéto , the succin ct succ is fum m oins high will era

( citr ate, Iso citrate, alph' acéto' glutarate, succin yl CoA, succ inate, fum arate, m alate, O xaloacétate)

Assessment of the cycle of Krebs

The cycle of Krebs is composed of 8 stages, each one is catalyzed by a specific Enzyme. During the cycle are produced, starting from a mole of Glucose and until the stage CO_{2 and H₂O:}

2 moles of CO₂
4 moles of NADH, H⁺
1 mole of FADH₂
1 mole of ATP. Attention, it is false to consider that the cycle of Krebs is very energy. Indeed, it produces from a point of view gross only one ATP, in the form of GTP, which is less than simple glycolysis (2 ATP). The cycle of Krebs is however POTENTIALLY energy when it is coupled with the respiratory chain mitochondriale (CRM). The cycle of citrate will reduce coenzymes (NAD and FAD) which will be oxidized thereafter by this CRM which via a gradient of concentration and a phenomenon of osmosis by enzyme ATP synthase will produce the 11 other allotted ATP, often by error, with only and single cycle of Krebs.

Assessment

$1Glucose + 10NAD^ {+} + 2FAD + 2ADP + 2GDP+ 4P_ {I} + 2:00 _ {2} O$ $\ rightarrow$ $6 CO_ {2} + 10 NADH, H^ {+} + 2FADH_ {2} + 2ATP + 2GTP$

What corresponds, after reduction of the Coenzyme S NAD and FAD by the respiratory Chaîne with 38 ATP (maximum theoretical possible) .

Conclusion, the use of glucose by aerobic Respiration is energy than the Fermentation S.

In the presence of a great quantity of acétylCoA, the cycle of Krebs can be overflowed in particular in the diabetics having a severe deficit out of insulin or after a prolonged Jeûne, to see Cétoacidose diabetic.

Regulation of the cycle

The irreversible stages of the cycle of Krebs can be controlled: stage of the citrate synthase, the isocitrate déshydrogénase and α-cétoglutarate déshydrogénase.

the citrate synthase is activated by the ADP but is inhibited by the NADH, the ATP and citrate. It thus is respectively inhibited by the reduction, the energy load and the product of the reaction which it catalyzes.
the isocitrate déshydrogénase is activated by calcium, the ADP and is inhibited by the NADH and the ATP.
L'α-cétoglutarate déshydrogénase is activated by calcium and is inhibited by the NADH, the ATP and its product the succinyl-CoA.

There is thus a regulation according to the availability of the substrate, the reduction, the concentration in product and the energy load. One can note that there is no regulation by covalence (phosphorylation of proteins).

See too

respiratory Chain: to become NADH, H+
Glycolysis
'' principal ways of the metabolism '' (on wikibooks)

External bond

the cycle of Krebs

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